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Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review

Published online by Cambridge University Press:  13 September 2011

P. A. Thompson ,
D. E. Wright ,
C. E. Counsell  and
J. Zajicek
P. A. Thompson*
Affiliation:
Centre for Health and Environmental Statistics, University of Plymouth, Plymouth, UK
D. E. Wright
Affiliation:
Centre for Health and Environmental Statistics, University of Plymouth, Plymouth, UK
C. E. Counsell
Affiliation:
University of Aberdeen, Division of Applied Health Sciences, Foresterhill, Aberdeen, UK
J. Zajicek
Affiliation:
Peninsula College of Medicine and Dentistry, Plymouth, UK
*
Correspondence should be addressed to: Dr Paul Thompson, Centre for Health and Environmental Statistics, University of Plymouth, ITTC Building Tamar, Science Park, Davy Road, Derriford, Plymouth, PL6 8BX. Email: paul.thompson1@plymouth.ac.uk.
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Abstract

Background: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate.

Methods: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol.

Results: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure.

Conclusions: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

Keywords

Alzheimer's diseaseclinical trialsstatistical analysissurrogate markersoutcome measures
Type
Review Article
Information
International Psychogeriatrics , Volume 24 , Issue 5 , May 2012 , pp. 689 - 697
Copyright
Copyright © International Psychogeriatric Association 2011

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